Positron emission tomography (PET) is an extremely effective imaging tool in preclinical and clinical cancer research to visualize physiological state or changes in the living body, to investigate the mechanism of disease, and to quantify biological processes such as receptor occupancy, cell proliferation, metabolic activity, apoptosis, and gene expression. Since PET allows measurement of phenotypic changes associated with a malignant condition with high sensitivity, the onset of a particular disease such as cancer can be detected, diagnosed, and treated at an early stage prior to the development of metastasis. Typically, 18F-labeled PET tracers are synthesized using nucleophilic fluorination of activated precursors with [18O]H2O/[18F]fluoride obtained from cyclotron. Due to high F-ion solvation energy, aqueous fluoride is inactive unless it is released from its aqueous surrounding. This is usually achieved by mixing aqueous fluoride with base (KHCO3, K2CO3 etc.) and phase transfer agent (e.g., Kryptofix-222) and azeotropic drying of the resulting solution with acetonitrile. The dried active complex (e.g., [18F]KF/K222) is further used for radiolabelling. Depending on technical method of fluoride activation (i.e. microchip or macro-reactor evaporation, cartridge solvent exchange), this procedure takes 20-30 minutes and some loss of initial radioactivity is observed.[4,5]
To reduce the need for a lengthy drying process, there has been interest during the last years in the development of radiofluorination methods that allow to use aqueous [18F]fluoride directly without the traditional drying/azeotroping step. Several novel approaches were suggested, such as enzymatic and transition-metal catalysis, development of specific substrates and fluorinating reagents. The majority of methods which are directly using the cyclotron-delivered [18O]H2O/[18F]fluoride leads to low-to-moderate fluoride conversion and yields of fluorinated product, while reactions are conducted in aqueous-organic medium with water content up to 20% and mostly these methods deal with aromatic nucleophilic fluorination. Titania is widely used in a variety of chemical processes, including electro- and photochemistry. Along with broad catalytic activity it possesses strong ability to adsorb water from the surrounding medium.
Provided herein, inter alia, is a conceptually new method based on titania as a catalyst. Embodiments include highly efficient and fast route for radiofluorination is suitable for aromatic, aliphatic and cycloaliphatic precursors in organic-aqueous medium with maximum tolerated water content up to 25%.